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Kidney Week

Abstract: SA-PO638

Effect of Serum Parathyroid Hormone on Tacrolimus Therapy in Kidney Transplant Patients: A Possible Biomarker for a Tacrolimus Dosage Schedule

Session Information

  • Pharmacology
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Fujimura, Rui, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
  • Watanabe, Hiroshi, School of Pharmacy, Kumamoto University, Kumamoto, Japan
  • Hirata, Kenshiro, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan, Kumamoto, Japan
  • Maruyama, Toru, School of Pharmacy, Kumamoto University, Kumamoto, Japan
Background

The mechanism responsible for the decreased extra-renal CYP3A activity in chronic kidney disease (CKD) patients remains unknown. Using an animal model, we previously found that elevated levels of serum intact parathyroid hormone (iPTH) caused a reduced CYP3A activity. The purpose of this study is to investigate whether serum iPTH levels affects the pharmacokinetics of tacrolimus, a CYP3A substrate, and its dosage schedule in kidney transplant recipients.

Methods

Thirty-four patients who were recipients of kidney transplantation between April 2014 and March 2016 and were administrated prolonged-release tacrolimus (Graceptor®, Astellas Pharm Inc.) once daily were the subjects of this study. Among the 34 patients, 22 patients had received the concomitant CYP3A substrate drug. To clarify the role of iPTH on the pharmacokinetics of tacrolimus, we performed the analysis using 12 patients who had not been administered concomitant CYP3A substrate drug.

Results

To investigate the relationship between serum iPTH levels and tacrolimus trough levels, we monitored the serum iPTH levels in patients before kidney transplantation. At this time point, serum iPTH levels in these subjects were increased, but with large deviations due to the difference in the patients' background such as the causes of and the progression of renal failure and complications. Therefore, we examined the correlation between serum iPTH levels and trough levels after the first oral administration of tacrolimus at 4 days before kidney transplantation. A significant positive correlation between serum iPTH level and the initial trough level for tacrolimus was found.This indicates that the tacrolimus trough level before transplantation was higher in patients with high serum iPTH levels as compared to patients with low iPTH values. These data suggest that CYP3A activity might be lower in patients with high serum iPTH levels, as was observed in the previous animal study, and that the initial trough level of tacrolimus could be predicted from serum iPTH levels before kidney transplantation.

Conclusion

Monitoring serum iPTH levels could predict the trough level for the initial administration of tacrolimus, and may serve as an index for the initial dose of tacrolimus in kidney transplantation patients.